Septins promote epithelial motility by reinforcing the crosslinking of lamellar stress fibers and the stability of nascent focal adhesions.

Summary Axon branching is fundamental to the development of the peripheral and central nervous system [1, 2]. Branches that sprout from the axon shaft are termed collateral or interstitial branches [3, 4]. Collateral branching of axons requires the formation of filopodia from actin microfilaments (F-actin) and their engorgement with microtubules (MTs) that splay from the axon shaft [4–6]. The mechanisms that drive and coordinate the remodeling of actin and MTs during branch morphogenesis are poorly understood. Septins comprise a family of GTP-binding proteins that oligomerize into higher order structures, which associate with membranes and the actin and microtubule cytoskeleton [7, 8]. Here, we show that collateral branching of axons requires SEPT6 and SEPT7, two interacting septins [9]. In the axons of sensory neurons, both SEPT6 and SEPT7 accumulate at incipient sites of filopodia formation. We show that SEPT6 localizes to axonal patches of F-actin and increases the recruitment of cortactin, a regulator of Arp2/3-mediated actin polymerization, triggering the emergence of filopodia. Conversely, SEPT7 promotes the entry of axonal MTs into filopodia, enabling the formation of collateral branches. Surprisingly, septins provide a novel mechanism for the collateral branching of axons by coordinating the remodeling of the actin and microtubule cytoskeleton.

Filamentous and microtubule-associated septin GTPases guide the reorganization of the microtubule network during epithelial cell polarization.

Novel septin 9 repeat motifs interact with the acidic C-terminal tails of β-tubulin to promote microtubule bundling and asymmetric neurite growth.

Highlights d Septins form a membrane-bound double ring in the midbody of telophase cells d Septin rings demarcate the membrane sites of ESCRT-III assembly d SEPT9 is required for ESCRT-III ring formation and expansion to cones d SEPT9 interacts with TSG101 for recruitment and assembly of ESCRT-II/-III subunits